After injury, human postnatal hearts do not recover appropriately because cardiomyocytes (CM) have a limited proliferation capacity. Accordingly, cell therapy has emerged as a new option for regenerating damaged myocardium. Although various stem or progenitor cells are reported as effective, obstacles include low efficiency for generating pure cardiomyocytes, low cell retention after being transplanted into the heart, immunologic incompatibility, and tumor formation. Thus, there is a need to find improved methods of treating heart injury.
Attempts have been made to directly reprogram somatic cells into CM-like cells using specific cardiac transcription factors (TFs) or miRNAs. Ieda et al. report reprogramming of fibroblasts into functional cardiomyocytes. Cell, 2010, 142:375-386. Qian et al. report in vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature, 2012, 485:593-598. Song et al. report heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature, 2012, 485:599-604. Chen et al. report inefficient reprogramming of fibroblasts into cardiomyocytes using gata4, mef2c, and tbx5. Circulation research, 2012, 111:50-55.
Jayawardena et al. report microRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circulation research, 2012, 110:1465-1473.
Cao et al. report ascorbic acid enhances the cardiac differentiation of induced pluripotent stem cells through promoting the proliferation of cardiac progenitor cells. Cell Research, 2012, 22:219-236.
Sun et al. report bone morphogenetic protein-4 mediates cardiac hypertrophy, apoptosis, and fibrosis in experimentally pathological cardiac hypertrophy. Hypertension, 2013, 61(2):352-60.
Chang & Guo report mesenchymal stem cell-like properties in fibroblasts. Cell Physiol Biochem, 2014, 34(3):703-14.
References cited herein are not an admission of prior art.